ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective: To investigate follow-up participation situation, negative conversion, and tuberculosis incidence among boarding junior and senior high school freshmen with latent tuberculosis infection(LTBI) in Zhuhai, so as to provide a reference for better LTBI management in school settings. Methods: A prospective cohort study enrolled 413 LTBI and 27 184 non LTBI boarding junior and senior high school freshmen in Zhuhai from September to October 2023. The LTBI group underwent follow up retesting at >3-6, >6-12, >12-24, >24 months after screening. The followup content included mycobacterium tuberculosis infection testing,chest X ray examination,and questionaire survey(basic demographic information, lifestyle, history of close contact with tuberculosis, and suspected symptoms of pulmonary tuberculosis). Follow-up participation, negative conversion, and tuberculosis incidence were analyzed. Rate was compared by using the Chi-square test, and factors associated with negative conversion were assessed by multivariate Logistic regression analysis. Results: Follow-up participation rates increased initially and then declined, with rates of 25.67% within >3-6 months, 37.05% within >6-12 months, 82.02% within >12-24 months, and 52.21% after 24 months. The overall negative conversion rate was 61.03%. The differences in the conversion rate to negative of mycobacterium tuberculosis infection detection among junior and senior high school freshmen in the LTBI group by different testing methods, school types, smoking history, sleep status, and academic stress were all statistically significant( χ 2=124.96, 22.70, 4.71, 6.31, 6.08, all P <0.05). Multivariate Logistic regression analysis identified testing methods, smoking history, and sleep status as factors associated with negative conversion ( OR =1.90-21.67, all P <0.05). The cumulative incidence of tuberculosis was 726.39 per 100 000 in the LTBI group versus 14.71 per 100 000 in the non-LTBI group ( RR =49.37, 95% CI =11.08-219.87, P <0.01). Conclusions Boarding junior and senior high school freshmen with LTBI in Zhuhai have a higher risk of tuberculosis than concurrent non-LTBI students; they therefore represent a priority group for tuberculosis prevention and control. Centralized follow up is recommended to improve participation, and high specificity methods should be used in follow up retesting and maintain consistency across assessments.

Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology* ; Molecular Structure ; Animals ; Isodon/chemistry* ; Humans ; Diterpenes/pharmacology* ; Plant Extracts/chemistry*

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

To analyze the clinical data of patients with recurrent Clostridioides difficile infection(rCDI)in the southwestern region,and help clinicians identify high-risk populations early and adopt appropriate treatment strate-gies.Methods Clinical data of rCDI cases from a tertiary first-class hospital in southwest China from July 2019 to June 2024 were collected,and their host-related risk factors,exogenous risk factors,treatment schemes,and end-point outcomes were analyzed.Results In the past five years,a total of 26 cases of rCDI were detected from a ter-tiary first-class hospital in southwest China,accounting for 4.04％of the total positive cases(n=643)detected during the same period.19.23％of the recurrent patients experienced a second recurrence.The median age of rCDI patients was 66.5 years old,with males accounting for 73.08％.The major comorbidity included diabetes mellitus(34.62％),malignant tumors(30.77％),and chronic renal diseases(23.08％).In the 8 weeks before the first on-set of rCDI in patients,the top three drugs used were β-lactam and enzyme inhibitor compound(69.23％),proton pump inhibitors(65.38％),and carbapenems(46.15％).In the initial treatment of recurrent patients,3.85％(1/26)of the cases were treated with metronidazole,19.23％(5/26)of the cases received non-standard vancomy-cin/norvancomycin treatment in usage or dosage,46.15％(12/26)of the cases received treatment with course less than 10 days.In the treatment of the first recurrence,34.78％(8/26)of the cases received treatment with course less than 10 days.Conclusion For elderly patients and patients with diabetes mellitus,malignant tumors,and chronic renal diseases,who have used β-lactam and enzyme inhibitor compound,proton pump inhibitors,carbapene-ms within 8 weeks before disease onset,standard dose and treatment course of vancomycin or norvancomycin are recommended under permitted conditions,so as to reduce the risk of recurrence.

Objective:To investigate the longitudinal stability of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Activity of Daily Living Scale (ADL).Methods:The longitudinal cognitive assessment results of 68 dementia patients admitted to the Dementia and Leukoencephalopathy Outpatient Clinic, Department of Neurology, Peking Union Medical College Hospital, from January 2021 to January 2024, were retrospectively analyzed, including the total and sub-items scores of the MMSE, MoCA, and ADL. Two different rules were applied to analyze the abnormality rates: rule 1, where the current test result being better than the previous one was considered an abnormality; rule 2, where the current test result being better than the previous average score was considered an abnormality (If a patient had only 2 cognitive assessments, rule 2 was considered the same as rule 1). Two rules were used to analyze the abnormality rates of the scales. The statistical analyses were repeated after excluding patients with possible anxiety and depression status.Results:In assessing the total score stability, MMSE showed the lowest abnormality rates [27.2% (31/114) under rule 1 and 29.8% (34/114) under rule 2], while MoCA had the highest abnormality rates [41.3% (26/63) and 46.0% (29/63), respectively]. The ADL abnormality rates were 27.7% (23/83) and 33.7% (28/83), respectively. Among MoCA sub-items, category cue, multiple choice cue, second memory trial, orientation, and clock showed higher abnormality rates [31.7%(20/63), 30.2%(19/63), 23.8%(15/63), 22.2%(14/63), 22.2%(14/63), respectively]. After excluding population with possible anxiety and depression status, the relative abnormality rates of MMSE and ADL sub-items did not significantly change, while the abnormality rate of orientation in MoCA sub-items decreased relatively.Conclusion:The MMSE and ADL exhibit good stability in long-term monitoring of dementia patients, serving as essential tools for assessing and following up cognitive changes.

Objective To investigate the current situation of frailty in patients with home peritoneal dialysis and analyze its influencing factors,so as to provide bases for early identification of high-risk groups and targeted clinical intervention.Methods From October to December 2024,205 home-based peritoneal dialysis patients under long-term follow-up at a tertiary A hospital in Zhongshan,Guangdong Province,were selected by convenience sampling.The General Information Questionnaire,Fried Phenotype Scale,Nutritional Risk Screening Tool,Exercise Self-Efficacy Scale,and Social Support Rating Scale were used to investigate the influencing factors of frailty in home-based peritoneal dialysis patients by ordinal logistic regression analysis.Results A total of 201 valid questionnaires were collected.The prevalence of frailty among home-based peritoneal dialysis patients was 24.3％,while 39.3％were in the pre-frailty stage,and 36.3％showed no frailty.0rdinal logistic regression analysis revealed that age,residence location,primary disease,sleep status,serum albumin concentration,and exercise self-efficacy level were influencing factors of frailty in the home peritoneal dialysis patients(P＜0.05).Conclusion The incidence of frailty in patients with home peritoneal dialysis is higher,and patients with advanced age,living in rural areas,other types of primary diseases,insomnia,low serum albumin concentration and low exercise self-efficacy are more likely to develop frailty.Specialist doctors and nurses of peritoneal dialysis should pay attention to the early screening of frailty in patients with peritoneal dialysis at home,and take personalized intervention measures to prevent or delay the occurrence of frailty according to the relevant risk factors.

OBJECTIVE To study regularity of different components whose skin permeability is enhanced by essential oils(EOs)from traditional Chinese medicine(TCM)with hot property.METHODS Five EOs from TCM with hot property,namely Galangal oil,Dried Ginger oil,Cinnamon oil,Pepper oil,and Evodia oil were prepared and used in further studies.The in vitro skin cytotoxici-ty of these EOs and chemical penetration enhancer(PE)Azone were compared.HPLC method was established to determine 9 TCM components that are usually used in permeation studies.And the in vitro permeation experiments were carried out using the modified Franz diffusion cell method to evaluate the penetration enhancement effects of five EOs.RESULTS The cytotoxicity test revealed the IC50 value of EOs was 3.63-8.15 times of that of Azone,the classical chemical PE.HPLC method showed perfect specificity and 9 TCM components performed well in linear relationship,precision,repeatability,stability,and average recovery rate.The results of multiple linear regression showed a significant association between the penetration enhancement effects of EOs from TCM with hot prop-erty and log P values of the TCM components.EOs from TCM with hot property showed satisfactory penetration enhancement effects for hydrophobic components with log P values in the range of 2.6-3.5,e.g.resveratrol,tetrahydropalmatine and quercetin.CONCLU-SION EOs from TCM with hot property should be reasonably selected as PE according to the oil-water partition coefficient of the in-gredients.

Objective:To develop and validate machine learning-based radiomics models using preoperative CT images for individualized prediction of mitotic index (MI) in patients with gastrointestinal stromal tumors (GIST).Methods:The study was a case-control study. The data of 348 GIST patients confirmed by pathology were retrospectively collected from two independent medical centers: the Affiliated Hospital of Qingdao University (center 1) and Shandong Provincial Hospital Affiliated to Shandong First Medical University (center 2), covering the period from January 2013 to June 2018. Patients from center 1 were divided into a training cohort (176 cases) and an internal validation cohort (75 cases) at a ratio of 7∶3 using random sampling. Patients from center 2 served as an independent external validation cohort (97 cases). The primary endpoint was MI, categorized into high MI (145 cases) and low MI (203 cases) groups. Radiomic features were extracted from the portal venous phase images of preoperative contrast-enhanced CT scans. Five machine learning algorithms, including logistic regression, support vector machine, random forest, decision tree, and extreme gradient boosting (XGBoost),were employed to construct MI prediction models. The optimal model was identified using receiver operating characteristic curves. An individualized prediction model was developed by integrating the the optimal machine learning model combined with selected independent clinical factors, and the importance of features was visualized using Shapley Additive Explanation (SHAP) analysis. Patients were followed up, and Kaplan-Meier curves along with log-rank tests were used to evaluate recurrence-free survival (RFS) differences between the predicted high MI and low MI groups.Results:Among the five constructed machine learning models, the XGBoost model demonstrated the best predictive performance, with area under the curve (AUC) of 0.809 (95% CI 0.738-0.872), 0.693 (95% CI 0.571-0.809), and 0.718 (95% CI 0.605-0.822) in the training cohort, internal validation cohort, and external validation cohort, respectively. An individualized prediction model combining the XGBoost model with independent clinical factors (tumor location and tumor size) was developed. The model achieved AUC of 0.843 (95% CI 0.785-0.899), 0.791 (95% CI 0.680-0.894), and 0.777 (95% CI 0.678-0.861) in the training cohort, internal validation cohort, and external validation cohort, respectively. SHAP analysis indicated that radiomic features had the highest predictive impact. In both the training cohort and internal validation cohort, the RFS of patients predicted to be in the high MI group was lower than that of the low MI group, with statistically significant differences ( χ2=14.58, 9.52, both P<0.001). However, there was no statistically significant difference in RFS in the external validation set ( χ2=6.18, P=0.080). Conclusions:The optimal XGBoost model based on radiomic features extracted from preoperative portal venous phase CT images, when combined with clinical factors, can effectively predict the MI of GIST patients.

BackgroundPostpartum depression （PPD） is a prevalent postpartum complications that significantly compromises women's psychological and physical well-being. Repetitive transcranial magnetic stimulation （rTMS）， a conventional neuromodulation technique， has been increasingly used in the treatment of PPD. However， high-quality evidence regarding its efficacy and safety remains limited. ObjectiveTo evaluate the efficacy and safety of rTMS in the treatment of PPD， thereby providing references for clinical treatment. MethodsDatabases including Cochrane Library， PubMed， Embase， CNKI， Wanfang， VIP and China Biology Medicine disc （CBM） were electronically searched for randomized controlled trials （RCTs） on rTMS for PPD， with the search spanning from database inception to February 8， 2025. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions 5.0.1， and the certainty of evidence was graded according to the Grading of Recommendations Assessment， Development and Evaluation （GRADE） approach. Meta-analysis was conducted using RevMan 5.3 and Stata 12.0. The outcomes of the Meta-analysis included the total effective rate， Edinburgh Postnatal Depression Scale （EPDS） score， Hamilton Depression Rating Scale （HAMD） score， and adverse reactions （dizziness， headache， nausea， diarrhea， and the overall incidence of adverse reactions）. ResultsA total of 11 studies involving 729 patients with PPD were included. Meta-analysis results showed that the total effective rate in the study group was significantly higher than that in the control group （OR=5.54， 95% CI： 3.07–10.01， P<0.01）. Both EPDS score （SMD=-2.38， 95% CI： -3.39–-1.37， P<0.01） and HAMD score （SMD=2.53， 95% CI： 1.21–3.85， P<0.01） in the study group were significantly lower than those in the control group， with statistically significant differences. Comparisons between the study group and control group reveal no significant differences in the incidence of dizziness and headache （RR=1.47， 95% CI： 0.63–3.43， P>0.05）， nausea （RR=1.46， 95% CI： 0.55–3.86， P>0.05）， diarrhea （RR=0.71， 95% CI： 0.23–2.20， P>0.05）， and overall adverse reactions （RR=1.30， 95% CI： 0.79–2.15， P>0.05）. GRADE assessment rated the four indicators of dizziness and headache， diarrhea， overall incidence of adverse reactions， and EPDS score as "moderate-certainty evidence"， and rated the total effective rate， nausea， and the HAMD score as "low-certainty evidence". ConclusionrTMS demonstrates certain therapeutic efficacy for PPD， with a safety profile comparable to conventional treatment. ［Funded by Sichuan Psychological Society Research Planning Project （number， SCSXLXH202403099）； Guiding Science and Technology Plan Project of Guangyuan （number， 23ZDYF0095）］